Tunneling Energy Effects on GC Oxidation in DNA Glenna S. M. Tong, Igor V. Kurnikov, † and David N. Beratan* Departments of Chemistry and Biochemistry, Box 90346, Duke UniVersity, Durham, North Carolina 27708-0346 ReceiVed: September 5, 2001; In Final Form: December 11, 2001 Hole-mediated electronic couplings, reorganization energies, and electron transfer (ET) rates are examined theoretically for hole-transfer reactions in DNA. Electron transfer rates are found to depend critically on the energy gap between the donor/acceptor states and the intervening basessthe tunneling energy gap. The calculated distance decay exponent for the square of the electronic coupling, , for hole transfer between GC base pairs (and pi-electron D/A pairs) ranges from 0.95 to 1.5 Å -1 in the model structures as the tunneling energy gap varies from 0.3 to 0.8 eV (which we argue is the range of energy gaps for GC oxidation probed in recent experiments). We show that the tunneling energy gap depends on the ET reorganization energy, which itself grows rapidly with distance for ET over 1-5 base pairs. Inclusion of the distance dependence of reorganization energies for these hole transfer reactions gives the tunneling rates an apparent decay exponent of ∼1.5-2.5 Å -1 . We show that ET rates observed in DNA across one and two base pairs are reasonably well described with single-step ET theories, using our calculated couplings and reorganization energies. However, the computed single-step tunneling (superexchange) ET rates for donor and acceptor species separated by three or more base pairs are much smaller than observed. We conclude that longer-distance ET probably proceeds through thermal population of intermediate hole states of the bridging bases. Switching between mechanisms as distance grows beyond a few base pairs is likely to be a general characteristic of ET in small tunneling energy gap systems. I. Introduction In the past decade, long-distance DNA electron transfer (ET) has received considerable experimental 1-43 and theoretical attention. 44-67 A fundamental understanding of these reactions has substantial implications for establishing the mechanism of DNA damage and repair, 68-71 as well as for designing DNA biological assays 72-75 and miniaturized electronic devices. 52,76-85 Our goal is to establish a quantitative physical framework for describing these reactions, based on a detailed molecular- modeling approach. Our specific focus is the nature of super- exchange-mediated coupling among native bases, modified bases, and π-electron reaction partners such as stilbene. ET in systems of this kind is probed in a large number of recent experiments 11,12,14,15,17-19,21,23,27,31-35,37-43 involving hole transfer to GC base pairs imbedded in AT runs. We will show that the strong electron-nuclear coupling characteristic of DNA ET leads to tunneling energy gaps of ∼0.5-1.0 eV between bridging and donor-acceptor states and, consequently, rapid decay of superexchange interactions with ET distance. There- fore, we expect (in this class of DNA ET experiments) a switching of the ET mechanism from superexchange to ther- mally activated hopping for donor-acceptor pairs separated by more than two base pairs. Tunneling versus Hoping. DNA mediated ET reactions display a wide range of distance dependencies, associated with apparent exponential decay constants from 0.1 to 1.5 Å -1 (the values at the extremes of this range remain somewhat uncertain as the primary kinetic processes are not easily probed). 1,9,12,14,15,17-19,24,26,27,31,36,40,41 A physical explanation of this wide range of observed distance dependences is that DNA ET can access either single step donor-to-acceptor tunneling (superexchange) or multistep hopping along the DNA bases. 45-48,51,57,59,65,86,87 If the donor and acceptor interact weakly, the electron-tunneling rate is often described by a nonadiabatic golden rule rate expression (in the high-temperature regime): 88 Here, H DA is the donor-acceptor interaction mediated by the bridging medium. The H DA superexchange interactions decay approximately exponentially with distance and lead to a rapid decay of tunneling ET rates with distance. Exponential decay constants for H DA 2 in proteins are ∼1.0-1.5 Å -1 , 89-91 and electron tunneling rates drop by about an order of magnitude each 1.0-3.0 Å. 91 Multistep hopping in DNA is possible if donor and/or acceptor groups can oxidize or reduce some of the bases. Rapid multistep hopping can proceed over much larger distance than single-step tunneling. 57,59 It is important to understand precisely how far and how fast an electron or hole may tunnel in DNA and what factors influence this tunneling process, to understand both single and multistep transport mechanisms. Even in multistep ET, the short distance steps may involve tunneling (if the reaction is nona- diabatic). This paper focuses on the specific structural and energetic aspects of DNA that influence the electron tunneling rates. DNA hole transfer systems under study in several labs employ donors and acceptors with redox potentials close to those of * Corresponding author. † Current address: Department of Chemistry, Northwestern University, Evanston, IL 60208. k ET non-ad ) 2π p |H DA | 2 1  4πλk B T exp [ - (∆G 0 + λ) 2 4λk B T ] (1) 2381 J. Phys. Chem. B 2002, 106, 2381-2392 10.1021/jp013387g CCC: $22.00 © 2002 American Chemical Society Published on Web 02/09/2002